Four VA funded investigators at the North Florida South/Georgia Veterans Health System at Gainesville Malcom Randall VA Medical Center (VAMC) are requesting a laser point scanning Confocal Microscope (LSM) with Airyscan made by Carl Zeiss to replace a 15-year old inoperable and outdated Confocal Microscope. This old system has been a part of the Research Service Core Equipment for this VAMC. This obsolete and non- functioning 2-photon system is too old to renew/salvage a service contact, and currently the manufacturer is unable to provide the assistance it needed to make it operational. It was a very useful system over many years for many investigators performing basic and translational research in this VAMC. Now it is not operational. Therefore, it has been a cherished desire of all investigators of this VAMC to replace this old system with a new Multi-Photon Confocal Microscope. Thus, the objective of this proposal is to obtain necessary funds to purchase a state-of-the-art Multi-photon confocal microscope system and to replace this old 2-photon system. The request includes all the necessary components of a new microscope system that can function as a complete system. Several factors make this ShEEP proposal very significant which include a) an existing dedicated location to house this microscope (no renovation or room modification is needed), b) an existing proven functional operating plan for day-to-day management and safe operation, c) a team of experienced users, and d) committed financial resources from the Research Service to maintain the service plan during post-warranty period. The proposed LSM 880 Multi-photon Confocal Microscope with Airyscan is a cutting-edge/ultramodern LSM system made by Carl Zeiss, Germany. The manufacturer graciously agreed to trade in our dilapidated old system with a significant $$ amount (see quote). This microscope provides extremely sensitive imaging and are particularly well suited to our VA researchers here in this VAMC. This system has the capability of generating 34-channel parallel imaging across the complete wavelength to monitor up to 10 dyes simultaneously to produce a beautiful image of a target tissue sample. The NLO multiphoton microscopy add-on for LSM 880 combines laser scanning functionality with Airyscan and an outstanding imaging depth by nonlinear Carl Zeiss optics to make this microscope a superior system. Since this proposed system is a part of Research Core facility, it will benefit all investigators of this VAMC. The participating VA investigators for this ShEEP request have VA appointments (minimum 5/8th) with VA space/resources at the Malcom Randall VAMC, and have joint appointment with the University of Florida as faculty member in the College of Medicine. All investigators are successful, productive and funded. Each investigator is experienced in attracting and training high caliber VA career development, predoctoral and postdoctoral level trainees, as well as mentoring the research careers of many young investigators. Each of the VA investigators is extensively accomplished in both academia and research. The dual affiliations provide an optimal setting with broad academic resources for education, research training, and research collaborations for each of the investigators individually and collectively. Although the needs for a modern confocal microscopic imaging system are always there, both individual investigators and the Research Service lack the ability to purchase such an innovative microscope system. This confocal microscope offers several advantages over conventional light optical microscopy and other modest confocal microscopy, including the ability to control depth of field, elimination or reduction of background information away from the focal plane and the capability to collect serial optical sections with three dimensional imaging from thick specimens. There has been a tremendous explosion in the popularity of confocal microscopy in recent years, due in part to its great number of applications in many areas of current research interest. This system will provide a progressive new dimension to this Research Service. Availability of this advanced/contemporary microscope, indeed, will facilitate research effort, collaboration and expand the research portfolio of this VAMC.